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• Nonvisualization of an IJV segment on noninvasive imaging is nonspecific. • Jugular venous compression, absence, and occlusion should be differentiated. • Invasive imaging should be considered when noninvasive imaging is indeterminate. The incidence and effects of stenosis of the cerebral venous system are poorly understood. When noninvasive computed tomography venography (CTV) of the head and neck suggests complete internal jugular vein (IJV) occlusion, invasive catheter-directed venography can discordantly show venous patency. We compared CTV vs digital subtraction venography (DSV) in the evaluation of patency/occlusion in the suspected IJV and contralateral IJV. We queried the venous intervention database of our U.S. academic tertiary-care hospital to identify patients with complete or near-complete IJV occlusion per CTV from March 1, 2019 to March 1, 2020. We included patients with both noninvasive and invasive imaging of the target segment and the contralateral IJV. Four patients had suspected occlusion of the IJV at the skull base. Invasive catheter-directed venography consisted of DSV to assess direction of flow and vessel caliber, as well as manometry proximal and distal to areas of suspected stenosis. DSV showed patency in all 4 IJVs for which CTV had shown suspected occlusions. CTV findings of the contralateral IJVs were patency (n = 2), moderate stenosis (n = 1), and severe/critical stenosis (n = 1). Contralateral IJV caliber, measured by DSV, was concordant with CTV findings. Median mean-pressure gradients across the apparent occlusion and contralateral segments were 1 (range, 1–4) mmHg and 0 (range, 0–5) mmHg, respectively. Although noninvasive CTV may suggest absence of or attenuated flow within the IJV, this technique may be insufficient to establish complete occlusion. Catheter-directed venography can be used to evaluate patency, vessel caliber, and mean-pressure gradient. [ABSTRACT FROM AUTHOR]

Traditional treatment for lumbar stenosis with instability is laminectomy and posterolateral arthrodesis, with or without interbody fusion. However, laminectomies remove the posterior elements and decrease the available surface area for fusion. Therefore, a sublaminar decompression may be a preferred approach for adequate decompression while preserving bone surface area for fusion. A retrospective review of 71 patients who underwent sublaminar decompression in conjunction with instrumented fusion for degenerative spinal disorders at a single institution was performed. Data collected included demographics, preoperative symptoms, operative data, and radiographical measurements of the central canal, lateral recesses, and neural foramina, and fusion outcomes. Paired t-tests were used to test significance of the outcomes. Thirty-one males and 40 females with a median age 60 years underwent sublaminar decompression and fusion. A median of two levels were fused. The mean Visual Analog Scale pain score improved from 6.7 preoperatively to 2.9 at last follow-up. The fusion rate was 88%, and the median time to fusion was 11 months. Preoperative and postoperative mean thecal sac cross-sectional area, right lateral recess height, left lateral recess height, right foraminal diameter, and left foraminal diameter were 153 and 209 mm 2 (p < 0.001), 5.9 and 5.9 mm (p = 0.43), 5.8 and 6.3 mm (p = 0.027), 4.6 and 5.2 mm (p = 0.008), and 4.2 and 5.2 mm (p < 0.001), respectively. Sublaminar decompression provided adequate decompression, with significant increases in thecal sac cross-sectional area and bilateral foraminal diameter. It may be an effective alternative to laminectomy in treating central and foraminal stenosis in conjunction with instrumented fusion. [ABSTRACT FROM AUTHOR]

Background context A persistent challenge in spine surgery is improving screw fixation in patients with poor bone quality. Augmenting pedicle screw fixation with cement appears to be a promising approach. Purpose The purpose of this study was to survey the literature and assess the previous biomechanical studies on pedicle screw augmentation with cement to provide in-depth discussions of the biomechanical benefits of multiple parameters in screw augmentation. Study design/Setting This is a systematic literature review. Methods A search of Medline was performed, combining search terms of pedicle screw, augmentation, vertebroplasty, kyphoplasty, polymethylmethacrylate, calcium phosphate, or calcium sulfate. The retrieved articles and their references were reviewed, and articles dealing with biomechanical testing were included in this article. Results Polymethylmethacrylate is an effective material for enhancing pedicle screw fixation in both osteoporosis and revision spine surgery models. Several other calcium ceramics also appear promising, although further work is needed in material development. Although fenestrated screw delivery appears to have some benefits, it results in similar screw fixation to prefilling the cement with a solid screw. Some differences in screw biomechanics were noted with varying cement volume and curing time, and some benefits from a kyphoplasty approach over a vertebroplasty approach have been noted. Additionally, in cadaveric models, cemented-augmented screws were able to be removed, albeit at higher extraction torques, without catastrophic damage to the vertebral body. However, there is a risk of cement extravasation leading to potentially neurological or cardiovascular complications with cement use. A major limitation of these reviewed studies is that biomechanical tests were generally performed at screw implantation or after a limited cyclic loading cycle; thus, the results may not be entirely clinically applicable. This is particularly true in the case of the bioactive calcium ceramics, as these biomechanical studies would not have measured the effects of osseointegration. Conclusions Polymethylmethacrylate and various calcium ceramics appear promising for the augmentation of pedicle screw fixation biomechanically in both osteoporosis and revision spine surgery models. Further translational studies should be performed, and the results summarized in this review will need to be correlated with the clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Pseudomeningoceles are extradural cerebrospinal fluid collections categorized into three groups: traumatic, congenital, and iatrogenic. Iatrogenic pseudomeningoceles occur after durotomy, usually after cervical or lumbar spine surgery. Although many remain asymptomatic, pseudomeningoceles can compress or herniate the spinal cord and nerve roots. We present a 57-year-old woman who had a thoracic laminectomy and discectomy. Two weeks after surgery, she presented with lower extremity weakness and gait difficulty. Physical examination revealed hyperreflexia and a T11 sensory level. MRI revealed a pseudomeningocele compressing the thoracic spinal cord. The patient underwent surgical drainage of the cyst. On follow-up, she had complete resolution of her symptoms, and MRI did not show a residual lesion. To our knowledge, this is the second documented post-operative pseudomeningocele causing symptomatic spinal cord compression of the thoracic spine. In this article, a review of the literature is presented, including four reported patients with post-traumatic pseudomeningocele causing myelopathic symptoms and 20 patients with iatrogenic pseudomeningocele that resulted in neurological decline due to herniation or compression of neural tissue. Treatment options for these lesions include conservative management, epidural blood patch, lumbar subarachnoid drainage, and lumbo-peritoneal shunt placement. Surgical repair, usually by primary dural closure, remains the definitive treatment modality for iatrogenic symptomatic pseudomeningoceles. [Copyright &y& Elsevier]

Comparative effectiveness research has a vital role in health reform and policies. Specialty training is one of these provider-side variables, and surgeons performing the same procedure who were trained in different specialties may have different outcomes. The objective of this study was to investigate the impact of spine surgeon specialty (neurosurgery vs. orthopedic surgery) on early perioperative outcome measures of elective anterior/lateral lumbar interbody fusion (ALIF/LLIF) for degenerative disc diseases. In a retrospective, 1:1 propensity score–matched cohort study, 9070 patients were reviewed from the American College of Surgeons National Surgical Quality Improvement Program database. Propensity score matching and subgroup analysis were used. In both groups (single-level and multilevel ALIF/LLIF), patients operated on by neurosurgeons had longer operative time (188 minutes vs. 172 minutes/239 minutes vs. 221 minutes); shorter total hospital stay (71 hours vs. 90 hours/89 hours vs. 96 hours); and lower rates of return to the operating room (2.1% vs. 4.1%/2.4% vs. 4.2%), nonhome discharge (8.7% vs. 11.1%/10.1% vs. 14.9%), discharge after postoperative day 3 (22.0% vs. 30.0%/38.0% vs. 43.9%), and perioperative blood transfusion (2.1% vs. 5.1%/5.0% vs. 9.9%) (P < 0.05). In multilevel ALIF/LLIF, patients operated on by neurosurgeons had lower readmission rates (3.9% vs. 6.9%) (P < 0.05). Other outcome measures and mortality rates were similar between the single-level and multilevel ALIF/LLIF cohorts regardless of surgeon specialty. Our analysis found significant differences in early perioperative outcomes of patients undergoing ALIF/LLIF by neurosurgeons and orthopedic surgeons. These differences have significant clinical and cost implications for patients, physicians, program directors, payers, and health systems. [ABSTRACT FROM AUTHOR]

Frailty has been shown to affect patient outcomes after medical and surgical interventions. The Hospital Frailty Risk Score (HFRS) is a growing metric used to assess patient frailty using International Classification of Diseases, Tenth Revision codes. The goal of this study was to investigate the impact of frailty, assessed by HFRS, on health care resource utilization and outcomes in patients undergoing surgery for spinal meningiomas. A retrospective cohort study was performed using the 2016–2019 National Inpatient Sample database. Adult patients with benign or malignant spinal meningiomas, identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, were stratified by HFRS: low frailty (HFRS <5) and intermediate-high frailty (HFRS ≥5). Patient demographics, hospital characteristics, comorbidities, procedural variables, adverse events, length of stay (LOS), discharge disposition, and cost of admission were assessed. Multivariate regression analysis was used to identify predictors of increased LOS, discharge disposition, and cost. Of the 3345 patients, 530 (15.8%) had intermediate-high frailty. The intermediate-high cohort was significantly older (P < 0.001). More patients in the intermediate-high cohort had ≥3 comorbidities (P < 0.001). In addition, a greater proportion of patients in the intermediate-high cohort experienced ≥1 perioperative adverse events (P < 0.001). Intermediate-high patients experienced greater mean LOS (P < 0.001) and accrued greater costs (P < 0.001). A greater proportion of intermediate-high patients had nonroutine discharges (P < 0.001). On multivariate analysis, increased HFRS (≥5) was independently associated with extended LOS (adjusted odds ratio [aOR], 3.04; P < 0.001), nonroutine discharge (aOR, 1.98; P = 0.006), and increased costs (aOR, 2.39; P = 0.004). Frailty may be associated with increased health care resource utilization in patients undergoing surgery for spinal meningiomas. [ABSTRACT FROM AUTHOR]

Comparative effectiveness research has a vital role in health reform and policies. Specialty training is one of these provider-side variables and surgeons who were trained in different specialties may have different outcomes upon performing the same procedure. To investigate the impact of spine surgeon specialty on early perioperative outcome of anterior cervical discectomy and fusion (ACDF). Retrospective, 1:1 propensity score-matched cohort study. A total of 21,211 patients who underwent ACDF between 2016-2018 were reviewed from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Outcomes included 30-day perioperative morbidity and mortality measures that are predefined in the ACS-NSQIP database. Patients were stratified by the specialty of surgeon performing the procedure (neurosurgery vs orthopedic surgery), and the number of levels operated on (single- vs multi-level surgery) Patients operated on by neurosurgeons were more likely to be older, smokers, of Hispanic ethnicity, functionally dependent, and to have higher BMI, an ASA class 3 or more, baseline dyspnea, bleeding disorders, and myelopathy. In both groups (single/multi-level ACDF), cases in the orthopedic surgery cohort were more likely to have shorter operation time (104 vs 133 minutes/ 138 vs 164 minutes), longer total hospital stay (41 vs 24 hours/ 46 vs 25 hours), higher return to operating room rates within the same admission (2.1% vs 0.7%/ 2.4% vs 0.6%), be discharged to destination other than home (4.6% vs 1.2%/ 4.9% vs 1.0%), be discharged after postoperative day 1 (11.9% vs 6.7%/ 18.9% vs 10.1%), higher perioperative blood transfusion rate (2.1% vs 0.4%/ 3.1% vs 0.6%) and higher sepsis rates (0.7% vs 0.2%/ 0.7% vs 0.1%). In the single-level ACDF group, cases in the orthopedic surgery cohort had higher readmission (4.1% vs 1.9%) and unplanned intubation rates (1.1% vs 0.1%). Other outcome measures and mortality rates were similar among the cohorts. Significant differences in early perioperative outcomes of patients undergoing ACDF by neurosurgeons and orthopedic surgeons were noted. These differences have significant clinical and cost implications for patients, physicians, payors and health systems. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

As of May 4, 2020, the coronavirus disease 2019 (COVID-19) pandemic has affected >3.5 million people and touched every inhabited continent. Accordingly, it has stressed health systems worldwide, leading to the cancellation of elective surgical cases and discussions regarding health care resource rationing. It is expected that rationing of surgical resources will continue even after the pandemic peak and may recur with future pandemics, creating a need for a means of triaging patients for emergent and elective spine surgery. Using a modified Delphi technique, a cohort of 16 fellowship-trained spine surgeons from 10 academic medical centers constructed a scoring system for the triage and prioritization of emergent and elective spine surgeries. Three separate rounds of videoconferencing and written correspondence were used to reach a final scoring system. Sixteen test cases were used to optimize the scoring system so that it could categorize cases as requiring emergent, urgent, high-priority elective, or low-priority elective scheduling. The devised scoring system included 8 independent components: neurologic status, underlying spine stability, presentation of a high-risk postoperative complication, patient medical comorbidities, expected hospital course, expected discharge disposition, facility resource limitations, and local disease burden. The resultant calculator was deployed as a freely available Web-based calculator (https://jhuspine3.shinyapps.io/SpineUrgencyCalculator/). We present the first quantitative urgency scoring system for the triage and prioritizing of spine surgery cases in resource-limited settings. We believe that our scoring system, although not all encompassing, has potential value as a guide for triaging spine surgical cases during the COVID pandemic and post-COVID period. [ABSTRACT FROM AUTHOR]

Background Context: Recently, preclinical and clinical studies suggest an association between renin-angiotensin system (RAS) blockers and bone healing, particularly in the context of osteoporotic bone fractures.Purpose: To determine the correlation between the use of RAS inhibitors and fusion outcomes and neurologic status in anterior cervical discectomy and fusion (ACDF) surgery.Study Design: Retrospective observational study.Patient Sample: Patients who underwent ACDF for degenerative disorders.Outcome Measures: Spinal fusion status and neurologic function (modified Japanese Orthopedic Association [mJOA] and Nurick grading scales).Methods: A retrospective chart review was performed, including 200 patients who underwent ACDF for degenerative disorders with 1-year minimum follow-up. Demographic data, comorbidities, antihypertensive medication, neurologic examination, and fusion status were collected. Spinal fusion was assessed via plain cervical x-ray, resorting to dynamic radiographs and/or computer tomography (CT) in cases of uncertainty. Preoperative mJOA and Nurick scores and recovery rates were calculated to determine neurologic status.Results: Of the 200 patients (42.5% females, 57.5% males, median age of 53.7 years), 82 hypertensive patients were identified. Seventy-seven (93.9%) were taking antihypertensive medication as follows: 36.4% angiotensin-II receptor blockers (ARBs), 35.1% angiotensin-converting enzyme inhibitors (ACEIs), and the remaining patients were taking other medication. In the analysis of fusion rates, patients treated with ARBs exhibited a higher fusion rate, while those treated with ACEIs displayed a lower fusion rate compared to untreated nonhypertensive patients (p = .04 and .02, respectively). The difference in fusion rates between ARBs and ACEIs was also significant, with the former displaying higher rates (p < .001). Smoking exhibited a negative correlation with spinal fusion (p < .001). In the multivariate analysis, ARBs remained an independent factor for successful fusion (p = .02), while smoking remained a risk factor for failed fusion (p = .002). In the neurologic examination, ACEIs, hypertension status, and older age correlated with lower modified Japanese Orthopedic Association (mJOA) recovery rates (p = .001, <.001, and <.001, respectively) in the univariate analysis.Conclusions: In ACDF patients, we observed that ARBs were associated with higher fusion rates. Conversely, ACEIs and smoking were related to failed fusion. Prospective case-control studies are needed to confirm these RAS inhibitors effects on spinal fusion. [ABSTRACT FROM AUTHOR]

Background Posterior atlantoaxial fusion is an important armamentarium for neurosurgeons to treat several pathologies involving the craniovertebral junction. Although the potential advantages of recombinant human bone morphogenetic protein-2 (rhBMP-2) are well documented in the lumbar spine, its indication for C1-C2 fusion has not been well characterized. In our institution, we apply rhBMP-2 to the C1-C2 joint either alone or with hydroxyapatite, locally harvested autograft chips, and/or morselized allogenic bone graft for selected cases—without conventional posterior structural bone graft. We report the clinical outcomes of the surgical technique to elucidate its feasibility. Methods We performed a single-center, retrospective review of data from 2008 to 2016 and identified 69 patients who had undergone posterior atlantoaxial fusion with rhBMP-2. The clinical records of these patients were reviewed, and the baseline characteristics, operative data, and postoperative complications were collected and statistically analyzed. Results The average age of the 69 patients was 60.8 ± 4.5 years, and 55.1% were women. With an average follow-up period of 21.1 ± 4.2 months, the C1-C2 fusion rate was 94.3% (65 of 69), and the average time to fusion was 11.4 ± 2.6 months (range, 5–23). The overall reoperation rate was 10.1% (7 of 69), with instrumentation failure in 7 patients (10.1%), adjacent segment disease in 2 (2.9%), and postoperative dysphagia and dyspnea in 2 patients (2.9%). No ectopic bone formation or soft tissue edema developed. Conclusions Although retrospective and from a single center, our study has shown that rhBMP-2 usage at the C1-C2 joint without posterior structural bone grafting is a safe and reasonable surgical option. [ABSTRACT FROM AUTHOR]

Background The pathogenesis of synovial cysts is largely unknown; however, they have been increasingly thought of as markers of spinal facet instability and typically associated with degenerative spondylosis. We specifically investigated the incidence of concomitant synovial cysts with underlying degenerative spondylolisthesis. Methods A literature search was performed using 4 online databases to assess the association between lumbar synovial cysts and degenerative spinal pathological features. Meta-analyses were performed on the prevalence rates of coexisting degenerative spinal pathological entities and treatment modalities. A random effects model was used to calculate the mean and 95% confidence intervals. Results A total of 17 studies encompassing 824 cases met the inclusion criteria. The pooled prevalence rates of concurrent spondylolisthesis, facet arthropathy, and degenerative disc disease at the same level of the synovial cysts were 42.5% (range, 39.0%–46.1%), 89.3% (range, 79.0%–94.8%), and 48.8% (range, 43.8%–53.9%), respectively. Among these, patients with coexisting spondylolisthesis were more likely to undergo spinal fusion surgery (vs. laminectomy alone) and reoperation than were patients without spondylolisthesis with a pooled odds ratio of 11.5 (95% confidence interval, 4.5–29.1; P < 0.0001) and 2.0 (95% confidence interval, 0.9–4.2; P = 0.088), respectively. Conclusions Patients with a combination of synovial cysts and degenerative spondylolisthesis are more likely to undergo spinal fusion surgery than laminectomy alone compared with patients with synovial cysts and no preoperative spondylolisthesis. Furthermore, patients with synovial cysts and spondylolisthesis are more likely to require additional fusion surgery. The results from the present review lend credence to the argument that synovial cyst herniation might be a manifestation of an unstable spinal level. [ABSTRACT FROM AUTHOR]

Background In sacropelvic fixation, the iliac screw technique offers biomechanically strong constructs, but its disadvantages include screw prominence, wound dehiscence, and postoperative pain secondary to the high profile nature. To overcome this drawback, S2-alar-iliac (S2AI) screws were developed as an alternative technique for sacropelvic fixation. This study aimed to compare the S2AI screw technique with the iliac screw technique in terms of postoperative symptomatic screw prominence. Methods A retrospective review of the records of sacropelvic fusion procedures performed at a single institution between October 2010 and January 2015 identified 32 patients with 72 iliac screws and 68 patients with 148 S2AI screws, and clinical and radiographic data were collected. If a patient had wound dehiscence and/or tenderness in the buttock immediately overlying a pelvic screw head postoperatively, it was defined as symptomatic screw prominence. The minimal distance from screw head to skin (MDSS) on postoperative computed tomography scans was measured for each patient to clarify the relationship between symptomatic screw prominence and MDSS. Results Mean follow-up period was 22.0 months. There was significantly more symptomatic pelvic screw prominence in the iliac screw group (11.1% vs. 1.4%, P = 0.002). MDSS ≤23 mm was the strongest predictor of symptomatic pelvic screw prominence, which yielded sensitivity of 100%, specificity of 94.1%, positive predictive value of 47.6%, and negative predictive value of 100%. Conclusions The use of the S2AI screw technique resulted in a reduced rate of symptomatic screw prominence. MDSS ≤23 mm was the strongest predictor of symptomatic screw prominence. [ABSTRACT FROM AUTHOR]

Existing literature demonstrates well-identified racial disparities in spine surgery outcomes. However, previous studies are of significant limitations. To investigate the association of race with 30-day perioperative complication rates of elective posterior spinal fusions (PSF) for adolescent idiopathic scoliosis (AIS). Retrospective cohort study. All pediatric patients with AIS who underwent PSF between 2012-2018 were reviewed from the (ACS-NSQIP) pediatric database. Thirty-day postoperative morbidity and mortality outcomes were analyzed. Complications included perioperative blood transfusion, venous thromboembolism, unplanned intubation, pneumonia, urinary tract infection, surgical site infection, sepsis, return to operating room, and death. Hospital course data, including operative time, the total length of hospital stay, the proportion of patients needed ICU admission, the proportion of patients discharged to other than home and discharged after the 4th postoperative day were also noted. Readmission data was included. These outcome variables are predefined in the ACS-NSQIP pediatric database, except for the discharge event after the 4th postoperative day, which was considered to be any discharge event occurring after a total hospital stay of 120 hours. Propensity score matching was used to determine whether race (ie, black vs white) had an influence on 30-day perioperative complications. A total of 4,051 PSF for AIS cases met inclusion criteria and were reviewed. Of these, 3221 (79.5%) patients were white and 830 (20.5%) were black. Patients in the black cohort were more likely to have higher BMI (23.8 vs 21.1), be of female gender (78.2% vs 74.5%), have an ASA class 3 or more (13.7% vs 11.1%), have asthma (8.3% vs 4.9%), have cardiac risk factors (5.1% vs 2.6%), use steroids (3.8% vs 1.1%). In the black cohort, 8% of the cases had up to 6 vertebral segments fused, 64.4% had 7-12 vertebral segments fused and 27.6% had 13 or more vertebral segments fused. In the white cohort, 15.9% of the cases had up 6 vertebral segments fused, 57.2% had 7-12 vertebral segments fused and 26.9% had 13 or more vertebral segments fused. After controlling for differences in baseline factors, except for the higher incidence of venous thromboembolism in the black cohort (2.8% vs 0.1%), (p <0.001), there were no significant differences in morbidity and mortality between the black and white cohorts. In contrast to prior literature, our analysis did not identify black race as an independent risk factor for higher perioperative morbidity or mortality in patients undergoing PSF for AIS, except for the higher incidence of venous thromboembolism. We believe that these results are important findings for clinicians and spine surgeons while counseling patients undergoing these types of procedures. It is important to address patient's concerns and to explain that the previously reported inferior perioperative morbidity and mortality outcomes in black patients might be due differences in baseline health status, and not due to the race difference itself. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Transplantation of adipose-derived mesenchymal stem cells (ADSCs) has become a promising approach for bone regeneration therapies, particularly in elderly patients. However, poor cell survival in vivo after implantation due to the ischemic tissue environment has been one of the major limitations of the effectiveness of this strategy. Hypoxia Inducible Factor-1α (HIF-1α) plays an important role in angiogenic-osteogenic coupling during bone regeneration, as it is a critical mediator of the adaptive cell response to hypoxia. DMOG treatment has been demonstrated to stabilize cellular expression of HIF-1α in cells, as well as enhance osteogenic and angiogenic capacity of MSCs. By therapeutically targeting both osteogenesis and vascularization via DMOG preconditioned MSCs, this tissue-engineering approach sought to yield superior bone quality and integration, thereby increasing rates of spinal fusion. We aimed to demonstrate that preconditioning adipose (ADSC)-derived (AD) MSCs with DMOG prior to implantation will prolong survival in vivo and improve spinal fusion outcomes in a rat model. In vivo study via a rat posterolateral spinal fusion model. Syngeneic 6-8 week old Lewis rats. Manual palpation scoring was performed by blinded researchers as follows: 0 = non-fused; 1 = partial fusion, some motion across operative joint; and, 2 = fused, no motion across the operated joint. MicroCT images were used to assess fusion mass volume (mm^3) via ImageJ software and determine CT fusion score (0 = non-fused; 1 = unilateral fusion; 2 = bilateral fusion). ADSCs were isolated from the inguinal fat pads of syngeneic 6-8 week old Lewis rats and cultured in vitro. When passage 1 (P1) ADSCs reached approximately 80% confluency they were pre-conditioned for 24 hours with 1 ng of DMOG (Fisher Scientific). After pre-conditioning, 2 × 10^6 ADSCs were seeded onto Vitoss (Stryker) bone graft substitute scaffolds for subsequent transplantation. Posterolateral spinal fusion surgery at L4-L5 was performed on 18 female Lewis rats divided into 2 experimental groups: [1] Vitoss+ADSCs pre-conditioned with DMOG; and, [2] Vitoss+non pre-conditioned ADSCs. Fusion was evaluated eight weeks post-surgery. Manual palpation scoring evaluated the motion across the operated joint, and MicroCT images were assessed for fusion mass volume and CT fusion. Preliminary microCT imaging data suggest that DMOG pre-conditioned ADSCs (n=12) yielded significantly higher fusion mass volumes than non-preconditioned ADSCs (n=6) (23.49 mm^3 vs. 15.39 mm^3, respectively, p=.001). DMOG pre-conditioned ADSCs showed a trend towards higher rates of fusion and manual palpation scores compared to non-conditioned ADSCs (1.16 vs. 0.50, respectively, p=.06; and 1.25 vs. 0.66, respectively, p>.05). In our rat posterolateral fusion model, DMOG pre-conditioned ADSCs displayed an increased fusion mass volume, CT fusion rates, and manual palpation score compared to non-conditioned ADSCs. Ongoing histological studies will evaluate whether there are any differences in the quality of bone formed within the fusion masses. Future studies will also compare whether these results are also similar in bone marrow-derived MSCs. Dimethyloxaloylglycine (Investigational/Not approved) [ABSTRACT FROM AUTHOR]

Approximately 132,000 patients per year undergo anterior cervical discectomy and fusion (ACDF) in the United States. Although the utilization of instrumentation and bone graft alternatives has enhanced fusion rates, pseudarthrosis remains a problem, with incidence rates up to 56%. Renin-angiotensin system (RAS) modulators are typically used to treat arterial hypertension, which affects 50-80% of spinal fusion patients. Recent evidence suggests an association between RAS blockers and bone metabolism, particularly in the context of bone healing. In addition, preclinical and clinical studies have suggested a potential correlation between the use of RAS blockers and reduced osteoporotic fracture risk. We aimed to determine whether there was a correlation between the use of antihypertensive medication, particularly angiotensin-II type-1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), and outcomes in anterior cervical discectomy and fusion (ACDF) surgery. Retrospective observational study. Degenerative disc disease patients who underwent ACDF. Spinal fusion status and neurological function (modified Japanese Orthopaedic Association [mJOA] and Nurick grading scales. A cohort of adult patients with symptomatic cervical degenerative disc disease who were operated upon using an allograft implant, and with a 1-year minimum follow-up was considered eligible. Information on demographic data, comorbidities (especially hypertension status), antihypertensive medication, neurological examination and fusion status were collected. Fusion criteria in static radiographs were increased opacification and bridging trabecular bone at the margins of the graft. In dynamic radiographs, fusion criteria were interspinous motion of < 1 mm and superjacent interspinous motion of < 4 mm. For CT scans, fusion was defined as solid bridging of bone across the disc space of the intended fusion. A total of 178 patients with cervical degenerative disc disease who underwent ACDF, with a median age of 53.7 (range 24-90) years, were included in the analysis. Median follow-up was 21.7 months. Out of the 82 hypertensive patients who were identified, 77 (93.9%) were taking antihypertensive drugs (28 [36.4%] received ARBs and 27 [35.1%] received ACEIs). The overall pooled fusion rate was 69.5%. Patients treated with ARBs exhibited a higher fusion rate compared to those who were untreated (88.9% vs 69.7%, respectively, p=.04). By contrast, patients treated with ACEIs displayed a lower fusion rate than untreated patients (45.8% vs 69.7%, respectively, p=.02). Comparisons between successful fusion and failed fusion groups identified treatment with ACEIs as risk factors for the development of pseudarthrosis. Treatment with ARBs displayed a trend towards being a favorable factor for fusion (RR=1.2, 95% CI 1.0, 1.5). In the multivariate nominal logistic analysis, ARB (p=.02) treatment remained an independent risk and beneficial factor, respectively, for fusion. In our retrospective study of a cohort of ACDF patients, treatment with ARBs was associated with an increased fusion rate, while treatment with ACEIs identified as risk factor for failed fusion. Further preclinical and clinical studies are needed to verify the beneficial effects of ARBs and deleterious influence of ACEIs on spinal fusion. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

BACKGROUND CONTEXT With the overall advancement in management of patients with human immunodeficiency virus (HIV) infection/AIDS, especially antiretroviral therapy regimens, HIV infection is now considered as a chronic disease and the longevity of these patients has significantly improved for the last two decades. As such, an increasing number of patients with HIV-infection are now potential candidates for elective surgical procedures such as spine surgery. In 2015, an estimated 1.1million adults and adolescents were living with HIV and 39,782 patients were newly diagnosed with HIV infection annually in 2016 (CDC data). Despite this increasing prevalence and incidence of the disease, the literature regarding clinical outcomes of spine surgery in patients with HIV is surprisingly scarce. As is the same as patients with other concurrent immunocompromising co-morbidities such as steroid use, diabetes mellitus, organ recipients, and/or chemo or radiation therapy, postoperative infection is one of the most concerning complications. Furthermore, bone mineral densities of HIV-infected patients are reported to be lower than noninfected controls, which could have some potential indications for worse long-term outcomes such as pseudoarthrosis. Thus, we aimed to characterize clinical outcomes of spine surgery in patients with HIV infection in order to facilitate judicious patient selection and comprehensive informed consent, which are of paramount importance in surgical decision-making processes for this high-risk cohort. PURPOSE Summarize clinical outcomes of spine surgery in patients with HIV, such as readmission rate, infectious complications, fusion rate, and mortality to address surgical indications for this specific cohort. STUDY DESIGN/SETTING Retrospective, single-center, propensity-matched cohort. PATIENT SAMPLE Patients who underwent spine surgery with HIV infection were included and compared with a matched-cohort without HIV infection OUTCOME MEASURES CD4 absolute count/uL, HIV-1 RNA copy numbers/mL, 30-day readmission rate, 90-day medical complication rate, one-year surgical site infectious complication rate, one-year fusion rate, and one-year mortality METHODS Single-center, retrospective data review from 2010 to 2016 yielded a total of 4,968 patients of spine surgery. Amongst those, 45 patients had HIV infection. Patients from the database were propensity-matched for age, sex, diagnoses, procedures, co-morbidities other than HIV at a 1:2 ratio, which yielded 90 matched-patients. Clinical outcomes of (A) 45 patients with HIV infection and (B) 90 matched-patients were compared and statistically analyzed. Intergroup comparison of binary variables was performed via Fisher's exact test. Intergroup comparison of continuous variables was achieved using unpaired t -tests. All reported p values are 2-sided and p values <.05 were regarded as statistically significant. RESULTS No statistically significant differences were noted for baseline characteristics including age, sex, diagnoses, procedures, and co-morbidities. There were no statistically significant intergroup differences in operative data such as operative time and operated levels. the HIV-infected patient group had higher rates of 30-day readmission (11.1% vs. 2.2%, P=.04), one-year surgical site infectious complication (13.3% vs. 3.3%, P=.06), and one-year pseudoarthrosis (17.8% vs. 4.4%, P=.02) as well as longer hospital stay (6.8days vs. 4.6days, p<.01) when compared with the control matched-cohort. Our post-hoc analysis only on 45 HIV-infected patients revealed that while HIV-1 RNA copy number with any cut-off values failed to predict 90-day medical complication rates, the cut-off value of CD4 absolute count <200/uL at the most recent preoperative encounter allowed us to stratify them into the two groups with regards to 90-day medical complication rates with statistical significance (44.4% (CD4<200) vs. 11.4% (CD4≥200), P=.04). CONCLUSIONS Spinal surgery in HIV-infected patients was associated with worse short- and long-term clinical outcomes, including higher rates of 30-day readmission, one-year infectious complication rate, and one-year pseudoarthrosis rate. Furthermore, CD4 absolute count may have some role in preoperative risk stratification. These results warrant further investigation of this cohort on multicenter, prospective basis, which should facilitate better patient selection for spine surgery and detailed informed consent, thereby potentially benefitting patients with HIV infection in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND CONTEXT Solid organ transplant is the mainstay of treatment for a wide variety of several end-stage organ diseases. The number of patients who will benefit from it is expected to increase due to improvement in distribution system for organs from donors, the discovery of novel immunosuppressive treatment/regimens, and better per- and post-operative management of these patients in general. Hence, an increasing number of these patients are becoming reasonable candidates for subsequent, elective surgeries such as spine surgery. Even though these patients are considered to be a high-risk group for surgery generally, clinical outcomes of spine surgery in patients with solid organ transplantation are not well-documented in the current literature partly due to its substantially rare incidence. Furthermore, prolonged use of steroids as well as immunosuppressant such as cyclosporine is associated with a decrease in bone mineral density. Thus, these outcome data might be of particular importance to consider surgical options for this high-risk cohort and inform them of specific risks and complications associated with spinal surgery after organ transplantation. PURPOSE Summarize clinical outcomes of spine surgery in solid organ recipients, such as readmission rate, infectious complications, and mortality, to facilitate clinical decision-making processes for this specific cohort. STUDY DESIGN/SETTING Retrospective, single-center, propensity-matched cohort. PATIENT SAMPLE Patients who underwent spine surgery at a single institution with previous history of solid organ transplantation were included and compared with a matched-cohort without solid organ transplantation. OUTCOME MEASURES Thirty-day readmission rate, 90-day medical complication rate, one-year infectious complication rate, one-year mortality, and functional outcomes such as ambulatory status, which was rated on a four-point scale (4, independently ambulatory; 3, requiring a cane; 2, requiring a walker; and 1, wheelchair bound). METHODS Single-center, retrospective data review from 2010 to 2016 yielded a total of 4,968 patients who underwent spine surgery. Amongst those, 28 patients had a previous history of solid organ transplantation. Patients from the database were propensity-matched for age, sex, body mass index (BMI), smoking status, diagnoses, procedures, co-morbidities other than diseases which had prompted organ transplantation at 1:2 ratio, which yielded 56 matched-patients. Clinical outcomes of (A) 28 patients with organ transplantation and (B) 56 matched-patients were compared and statistically analyzed. Intergroup comparison of binary variables was performed via Fisher's exact test. Intergroup comparison of continuous variables was achieved using unpaired t -tests. All reported p values are 2-sided and p values <.05 were regarded as statistically significant. RESULTS Baseline characteristics including age, sex, BMI, smoking, diagnoses, procedures, and co-morbidities (ASA scale) were similar between the two groups with no statistically significant difference, which validated our matching methods. There were no statistically significant intergroup differences in operative data such as operative time, estimated blood loss, operated levels, and use of bone morphogenetic protein-2. In terms of functional outcomes, postoperative improvement in ambulatory status was comparable between the two groups (A) 16.7% vs. (B) 18.1%, p>.99). However, the organ-recipient group resulted in longer hospital stays (A) 7.2days vs. (B) 4.3days, p<.01), higher rates of 30-day readmission (A) 14.3% vs. (B) 7.1%, P=.04), 90-day medical complication (A) 42.8% vs. (B) 17.9%, P=.02), one-year infectious complication (A) 14.3% vs. (B) 3.6%, P=.09), one-year reoperation (A) 14.3% vs. (B) 3.6%, P=.09) as compared with the control matched-cohort. CONCLUSIONS Spinal surgery after solid organ transplantation resulted in substantially increased complication rates when compared with the matched-control group, while other variables such as baseline characteristics, operative data, and functional outcomes were similar between the two groups. Careful patient selection, meticulous perioperative care, and thorough informed consent of potential complications would be imperative when performing spine surgery on this cohort. [ABSTRACT FROM AUTHOR]

Pedicle screws (PSs) are routinely used for stabilization to enhance fusion in a variety of spinal diseases. Although the accuracy of different PS placement methods has been previously reported, most of these studies have been limited to 1 or 2 techniques. The purpose was to determine the current accuracy of PS placement among 4 modalities of PS insertion (freehand [FH], fluoroscopy-assisted [FA], computed tomography navigation–guided [CTNav], and robot-assisted [RA]) and analyze variables associated with screw misplacement. A systematic review was performed of peer-reviewed articles reporting PS accuracy of 1 technique from January 1990 to June 2018. Accuracy of PS placement, PS insertion technique, and pedicle breach (PB) data were collected. A meta-analysis was performed to estimate the overall pooled (OP) rates of PS accuracy as a primary outcome, stratified by screw insertion techniques. Potential determinants were analyzed via meta-regression analyses. Seventy-eight studies with 7858 patients, 51,161 PSs, and 3614 cortical PBs were included. CTNav showed the highest PS placement accuracy compared with other techniques: OP accuracy rates were 95.5%, 93.1%, 91.5%, and 90.5%, via CTNav, FH, FA, and RA techniques, respectively. RA and CTNav were associated with the highest PS accuracy in the thoracic spine, compared with FH. The OP data show that CTNav has the highest PS accuracy rates. Thoracic PSs were associated with lower accuracy rates; however, RA showed fewer breaches in the thoracic spine compared with FH and FA. Given the heterogeneity among studies, further standardized and comparative investigations are required to confirm our findings. [ABSTRACT FROM AUTHOR]

BACKGROUND CONTEXT The surgical management of deformity, degenerative pathology, neoplasms, trauma and infection in the lumbosacropelvic spine remains a challenge due to high mechanical demand around this area, risks of pseudarthrosis, and invasive nature of the procedures. To date, two instrumentation techniques are primarily available: iliac screws (ISs) and S2-alar-iliac (S2AI) screws. Previous articles demonstrated lower rates of complications with S2AI screws as compared to ISs; however, none of them have focused on elderly patients who may harbor significant comorbidities, and as such, require more meticulous perioperative management, given these invasive and lengthy procedures. PURPOSE To report safety profile of S2AI in patients over 60 and address differences between S2AI screws and ISs. STUDY DESIGN/SETTING Single-center, retrospective, case-control study. PATIENT SAMPLE Single center, retrospective cohort who underwent lumbosacropelvic fixation with more than two-year follow-up. OUTCOME MEASURES Rates of complications such as mortality, unplanned reoperation, cardiorespiratory complications, transfusion-related complications and functional outcome measures such as visual analogue scale for back pain. METHODS Between October 2010, and December 2014, 171 sacropelvic fusion procedures with IS or S2AI screw instrumentation were performed in 161 patients. The inclusion criteria for this study were as follows: (1) patients over 60years old and (2) patients with more than two-year follow-up periods, which yielded 15 patients (IS) and 41 cases (S2AI), respectively. Rates of complications such as mortality, unplanned reoperation, pseudoarthrosis, cardiorespiratory complications, transfusion-related complications and functional outcome measures such as visual analogue scale for back pain and ambulatory status were collected and statistically analyzed. Intergroup comparison of binary variables was performed via Fisher's exact test. Intergroup comparison of continuous variables was achieved using unpaired t-tests. For the analyses on pain and functional outcomes, the perioperative comparisons for each group and intergroup comparisons were conducted using the Wilcoxon signed-rank test and the Mann–Whitney U test, respectively. All reported p values are 2-sided and p values <.05 were regarded as statistically significant. RESULTS Baseline characteristics such as age, sex, smoking history, diagnoses and comorbidities were similar in both groups. The S2AI group had lower rates of reoperation (19.5% vs 66.6%, p=.002), surgical site infection (0% vs. 16.0%, p<.001), wound dehiscence (0.0% vs. 20.0%, p<.001) and postoperative hyperkalemia (17.7% vs. 43.8%, p=.04) and had lower volume of estimated blood loss (EBL) [ml] (1817.5vs. 2775.6, p=.01) and transfused red blood cell units (4.6vs. 8.0, p=.001) than the IS group, while rates of mortality, L5-S1 pseudarthrosis, and other cardiorespiratory complications were similar in both groups. Pain relief and functional recovery were achieved in both groups without any significant intergroup differences. On multivariate analyses, use of S2AI screws over ISs, smoking, and operated levels were independent predictors of volume of transfusion. CONCLUSIONS Use of S2AI screws over ISs in the elderly was associated with lower rates of reoperation, surgical site infection, wound dehiscence and lower volume of EBL and RBC transfusion, while achieving similar clinical and functional outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND CONTEXT Occipitocervical fusion is the gold standard stabilization method for several pathologies involving craniovertebral junctions, including basilar invagination, atlantoaxial trauma and neoplasm. However, its postoperative clinical course is oftentimes complicated by dysphagia and dyspnea, presumably due to loss of mobility across occiput-C1-C2 joints, which could lead to aspiration pneumonia and acute airway obstruction, respectively, and are life-threatening complications in this procedure. The exact mechanism and its predictors still remain widely unstudied, but a previous article involving healthy volunteers elaborated on the importance of the occipital and external acoustic meatus to axis angle (O-EAa, "the angle formed by the McGregor line and the line connecting the external acoustic meatus and the midpoint of the inferior end plate of C2"), when predicting the narrowest oropharyngeal airway space (nPAS, "the narrowest anterior–posterior distance from the posterior pharyngeal wall to the back of the tongue between the levels of the uvula tip and the epiglottis tip") on X-rays, which theoretically should directly correlate with postoperative dysphagia. Here, we aimed to evaluate whether pre- and postoperative radiographical measurements such as O-EAa and nPAS could predict postoperative dysphagia in adult patients who underwent occipitocervical fusion procedures. PURPOSE To identify predictors of postoperative dysphagia in patients with adult occiptocervical fusion surgery. STUDY DESIGN/SETTING Retrospective, single-center. PATIENT SAMPLE Patients who underwent occipitocervical fusion at a single institution. OUTCOME MEASURES Prolonged postoperative dysphagia (more than 30 days). METHODS Single-center, retrospective data review from 2010 to 2016 identified 57 patients who underwent spine surgery involving occipitocervical fusion procedures. Among those, 51 patients had more than one-year follow-up as well as an adequate postoperative assessment of swallowing functions. Clinical records of those 51 patients (average age: 53.3, female: 54%) were collected and statistically analyzed. A total of 16 patients (31.4%, group (A)) were diagnosed with postoperative dysphagia associated with occipitocervical fusion, who were compared with 35 patients without this complication (group (B)) in terms of baseline characteristics, operative data and radiographical findings including perioperative O-EAa and nPAS at patients' neutral positions. Intergroup comparison of binary variables was performed via Fisher's exact test. Intergroup comparison of continuous variables was achieved using unpaired t -tests. ROC curves were drawn to evaluate the diagnostic value of O-EAa and nPAS for postoperative dysphagia. Furthermore, the Pearson's correlation was assessed between O-EAa and nPAS. Finally, a multilinear regression model was created to identify factors influencing nPAS. All reported p values are two-sided and p values <.05 were regarded as statistically significant. RESULTS There were no statistically significant difference in terms of baseline characteristics including age, sex, BMI, smoking and comorbidities or operative data such as estimated blood loss, operative time and operated levels. While preoperative O-EAa and nPAS were similar between the two groups (P=.39 and.55, respectively), postoperative O-EAa ((A) 89.3° versus (B) 104.5°, p<.01) and nPAS ((A) 9.9 mm versus (B) 13.6 mm, P=.01) as well as perioperative changes in O-EAa ((dO-EAa), (A) −4.1° vs. (B) 0.6°, P=.01) and nPAS (dnPAS, (A) −2.0 mm vs. (B) 0.2 mm, P=.01) were significantly different. The cut-off value of dOEA-a <−2.4° to predict postoperative dysphasia yielded sensitivity of 81.8% and specificity of 100% (AUC=0.939), which was comparable to dnPAS >−1.1 (sensitivity 81.8%, specificity 100%). The Pearson's correlation coefficient between these two parameters were 0.747 (p<.001). In a linear regression analysis, nPAS (mm) was found to be affected by O-EAa (estimate=0.2, P=.04) and sex (estimate=−4.8 (female=1), P=.03), but not by BMI in this model (R square=0.42). CONCLUSIONS Perioperative changes in O-EAa and nPAS were associated with postoperative dysphagia. Intraoperatively, O-EAa measurement on fluoroscopic images could be utilized as a surrogate marker for nPAS, thereby potentially allowing us to decrease the risk of this crucial complication. These data may prompt multicenter, prospective studies to further validate them and translate them into better patient care in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND CONTEXT With the advent of immunotherapy (IT) against various cancers, its applications to other cancers have been extensively investigated. However, it has been a challenge to apply IT to chordomas, due to lack of clinically-translatable in vivo models. Unlike othercancers that have been extensively studied from the immunotherapeutic standpoint such as melanomas, currently, there are no well-established murine chordoma cell lines that can be injected to syngeneic mice or transgenic mouse models that develop chordomas spontaneously, which prevents us from investigating the interaction between murine chordomas and murine immune cells. Meanwhile, in the field of immunology, the development of humanized mouse models, where a human immune system is incorporated into immunodeficient mice by engrafting them with human hematopoietic stem cells and fetal thymus, has emerged as a state-of-the-art technique, which allows researchers to investigate human immune system in vivo in the context of several immunological disorders including cancer. To scrutinize IT against chordoma, the development of this model is imperative. PURPOSE We aimed to develop a humanized mouse model engrafted with chordoma cells to study the interaction between humanimmune system and human chordomas. We also sought to utilize it to investigate synergistic effect between IT and radiation therapy (RT) against chordoma. STUDY DESIGN/SETTING Animal experiments. OUTCOME MEASURES Tumor size, cell subpopulations of tumor infiltratinglymphocytes, and cytokine levels in blood and tumors in each treatment group. METHODS Fifteen 10-12-week-old NSG mice, which lacks mouse T cells, B cells, and NK cells as well as functional mouse macrophages, were sub-lethally (1.5Gy) irradiated and then implanted with human fetal thymic tissue and CD34+ stem cells that had been harvested from a fetus, whose HLA-type is partially-matched with that of the U-CH1 chordoma cell line. Reconstitution of immune cells in NSG mice was confirmed 8 weeks posttransplantation and then each animal (15 humanized NSG mice and 12 naive NSG mice) was injected with U-CH1 cell suspension bilaterally and subcutaneously. Next, they were treated for 4 weeks as follows: (A) control, isotype antibodies (Abs) injection (n=3), (B) anti-human-PD-1 Abs (n=4), (C) RT + isotype Abs (n=3, unilaterally to the left-sided tumor, 8Gy × 4), (D) anti-human-PD-1 Abs and RT (n=5), (E) naive NSG mice (n=6, without the engraftment of human immune cells) + isotype, and (F) naive NSG mice (n=6) + anti-human-PD-1 Abs. During and after the treatment, anti-tumor activities were monitored via tumor size, flow cytometry, qRT-PCR, and immunohistochemistry. The data were statistically analyzed and p < 0.05 was set as statistically significant. RESULTS On average, human peripheral blood mononuclear cells (PBMCs) of 43.8% among all PBMCs (human + mouse), human T cells of 23.4% among human PBMCs, human CD8+ T cells of 24.3% among human T cells, and other lymphocytes such as B cells, macrophages, and NK cells were observed in peripheral blood of humanized mice via flow cytometry. One week after the treatment, on the irradiated side, (D) demonstrated lowest tumor volume ((A) 2220.0mm3, (B) 615.8mm3, (C) 1259.0mm3, (D)144.0mm3, p<.001), highest number of human PBMCs, highest % of CD8+ human T cells ((A) 31.0%, (B) 60.3%, (C) 43.0%, (D) 71.2%, p<.001), highest % of CD45RO+CD4+ (memory) human T cells ((A) 47.0%, (B) 56.5%, (C) 48.0%, (D) 65.4%, p<.001), and lowest % of PD−1+CD8+ (exhausted) human T cells ((A) 61.0%, (B) 42.5%, (C) 60.0%, (D) 36.6%, p<.001) in the tumors via flow cytometry, and highest IFN-gamma in the tumors via qRT-PCR, compared to the other five groups with statistical significance. On the nonirradiated side, similarly (D) had the smallest tumor compared to the others (P=.09). There were no statistically significant differences in tumor volume amongst (A), (E), and (F), suggesting that HLA-partially-mismatched immune cells from the fetus did not influence U-CH1 growth (immune tolerance) and that anti-human-PD-1 Abs we administered were efficacious only in the humanized mice. Currently, immunohistochemistry is being performed to further confirm the findings via the other modalities as described above. CONCLUSIONS We demonstrated that this humanized mouse model could be a revolutionary platform to investigate IT against rare cancers such as chordomas, where murine equivalent cell lines are not available to date, which hinders us from utilizing syngeneic or transgenic mouse models to study IT against cancers. The direct synergistic effect between IT and RT against chordoma as well as the potential abscopal effect was observed. [ABSTRACT FROM AUTHOR]